1. Field of the Invention
The invention relates to methods and systems for performing molecular comparisons.
2. Description of the Related Art
Recent efforts to reduce the time and effort required to identify safe and effective pharmaceuticals have focused in part on attempts to characterize the behavior of drug candidate molecules without the need to actually perform chemical tests on the compounds. Generally, these efforts have focused on the prediction of molecular behavior by a computational analysis of chemical structure. Although this approach has not eliminated the need to perform chemical experiments, the amount of such testing can be considerably reduced by early identification of promising leads, and by eliminating from consideration compounds which are extremely unlikely to exhibit a particular desired chemical activity.
In many methods of computational analysis, physical molecular characteristics are reduced to a set of one or more descriptors. In some cases, the descriptor is related to a molecular characteristic that has been correlated to a certain chemical trait or behavior. One such example is molecular polar surface area, typically defined as the exposed van der Waals surface area of oxygen and nitrogen atoms (and attached hydrogens) in a molecule.
In some techniques, a set of molecules having unknown biochemical behavior is compared to a molecule having known biochemical behavior. Molecules that are in some sense more “similar” to the molecule with known activity are predicted to be more likely to exhibit similar chemical behavior.
One commonly used evaluation process of this type involves comparing the spatial arrangement of similar atoms in the two molecules. Although conceptually simple, this comparison process is difficult to implement due to the difficulty in ensuring an optimal relative orientation of the two molecules prior to any comparison of their atomic arrangements. Some attempts to simplify this comparison process have involved projecting a three dimensional molecule onto a two-dimensional plane, and performing a comparison of two-dimensional projections. This reduces the above mentioned orientation problem, but does not eliminate it entirely, as relative translation and rotation must still be optimized before a valid comparison can be made.
To date, analyzing large libraries of compounds using the above mentioned techniques remains time consuming and computationally expensive. Accordingly, the drug discovery process would be improved by new techniques to computationally evaluate potential chemical activity that operate faster, and that can screen chemical libraries with a smaller investment in time and/or processing power.